The presence of autoimmune diseases, such as myasthenia gravis (MG), should not be seen as a not be seen as a factor against treatment with immune checkpoint inhibitors in patients with advanced metastatic cancer, a case report says.
The case report, “Metastatic Merkel cell carcinoma and myasthenia gravis: contraindication for therapy with immune checkpoint inhibitors?,” was published in the Journal for ImmunoTherapy of Cancer.
Checkpoint blockade immunotherapies are based on the principle of removing the “brakes” of our immune system and using its power to fight cancer faster and more effectively.
These include anti-PD1 immunotherapies, which have been developed to block the activity of the PD-1 receptor found on the surface of T-cells (the killers of our immune system), so that cancer cells fail to evade being targeted and eliminated by these immune cells.
Although anti-PD1 checkpoint inhibitors are promising candidates for the treatment of patients with Merkel cell carcinoma (MCC), an aggressive type of skin cancer, their use is associated with an increased risk of immune-related adverse events (side effects), especially flare-ups of pre-existing autoimmune disorders.
“In the literature, 23 cases of MG after immunotherapy with checkpoint inhibitors have been described, the majority being de novo [new] cases (72.7%), but also some cases of exacerbations of a preexisting MG (18.2%) or subclinical MG (9.1%). Only limited experience exists regarding therapy with immune-checkpoint inhibitors in patients with preexisting autoimmune disorders, as they are often excluded from clinical trials,” the investigators wrote.
In this case report, study authors described the clinical case of a patient with advanced metastatic MCC and MG who was successfully treated with the anti-PD1 inhibitor Keytruda (pembrolizumab), while avoiding undesirable immune-related side effects.
In 2005, the 61-year-old woman was diagnosed with MG and was receiving a combination of the immunosuppressant azathioprine and the acetylcholine esterase inhibitor Mestinon (pyridostigmine, by Valeant Phamaceuticals, after having undergone a thymectomy (surgical removal of the thymus).
In 2016, she was diagnosed with MCC, and within six months of her diagnosis, the tumor already had spread through her body, reaching lymph nodes and the spleen. As a result, her immunosuppressive treatment regimen was changed to mycophenolatmofetil (MMF), and in November 2016 she was started on Keytruda.
Because MMF was extremely toxic for her liver, she was switched to cyclosporine A (CsA), and within six weeks her liver transaminases (enzymes that when elevated may indicate liver inflammation or damage) had returned to normal levels.
After completing six cycles of Keytruda, the patient achieved a partial response (significant decrease in tumor size, with no signs of cancer spreading). At follow-up, 65 weeks after completing treatment with Keytruda, she was still in partial remission and had not experienced any MG flare-ups.
“Patients with a preexisting MG can be considered for treatment with immune checkpoint inhibitors if they have a life-threatening cancer and if other effective, long-lasting treatment options are not available. The risks and benefits of therapy should be weighed in a multidisciplinary setting and should be discussed thoroughly with the patient. Exacerbation of underlying MG can be potentially life-threatening and requires close monitoring in collaboration with neuromuscular specialists,” the authors wrote.